Currently used rodent
tumor models, including transgenic
tumor models, or subcutaneously-growing human
tumors in immunodeficient mice, do not sufficiently represent clinical
cancer, especially with regard to
metastasis and
drug sensitivity. In order to obtain clinically accurate models, we have developed the technique of surgical orthotopic implantation (SOI) to transplant histologically-intact fragments of human
cancer, including
tumors taken directly from the patient, to the corresponding organ of immunodeficient rodents. It has been demonstrated in 70 publications describing 10
tumor types that SOI allows the growth and metastatic potential of the transplanted
tumors to be expressed and reflects clinical
cancer. Unique clinically-accurate and relevant SOI models of human
cancer for antitumor and antimetastatic
drug discovery include: spontaneous SOI bone metastatic models of
prostate cancer,
breast cancer and
lung cancer; spontaneous SOI liver and lymph node ultra-metastatic model of
colon cancer, metastatic models of pancreatic, stomach, ovarian, bladder and
kidney cancer. Comparison of the SOI models with transgenic mouse models of
cancer indicate that the SOI models have more features of clinical metastatic
cancer.
Cancer cell lines have been stably transfected with the jellyfish
Aequorea victoria green fluorescent protein (GFP) in order to track
metastases in fresh tissue at ultra-high resolution and externally image
metastases in the SOI models. Effective drugs can be discovered and evaluated in the SOI models utilizing human tumor cell lines and patient
tumors. These unique SOI models have been used for innovative
drug discovery and mechanism studies and serve as a bridge linking pre-clinical and clinical research and
drug development.